Oxidation of organic compounds with a chromic oxidizing agent



United States Patent OXIDATION OF ORGANIC COMPOUNDS WITH A CHROMICOXIDIZING AGENT Nicholas Thomas Farinacci, New York, N. Y.

No Drawing. Application September 15, 1953, Serial No. 380,369

12 Claims. (Cl. 260-376) This application is a continuation in part ofmy copending application Serial No. 153,987, filed April 4, 1950, andnow abandoned in favor hereof.

This invention relates to improvements in the oxidation of suitableorganic compounds with oxidizing chromium compounds in a manner wherebythe reduced forms of the oxidant are continuously removed from thereaction zone and solution as an inert solid phase in the course of theoxidation. Particularly the invention relates to a method of oxidizingselected organic compounds with oxidizing chromium compounds which ischaracterized by carrying out the oxidation in the presence of an agentwhich continuously removes substantially all of the trivalent chromicion from the reaction zone and solution phase. More particularly theimproved process relates to the oxidation of suitable organic compoundswith an oxidizing chromium compound in the presence of an orthophosphateion producing compound whereby the trivalent chromic salts arecontinuously and completely separated from the reaction zone andsolution and thereby rendered inert and readily separable. Severaladvantages result from such removal which include steady oxidationpotentials, economies resulting from simplified operations and lowerconsumption of materials. At the same time this removal generallyimproves operating conditions so that more complete conversions andhigher yields of valuable products are obtained.

Chromic acid oxidation is frequently used in the tine chemical industryto manufacture oxygenated organic materials which are valuableintermediates for the production of hormones, dyestuifs, condiments andperfumcs. Numerous procedures utilizing chromic acid have been describedto degrade steroid side chains and to convert benzenoid hydrocarbons toquinones, ketones and acids.

Such processes invariably are complicated by the accumulation of largeamounts of soluble chromic salts and water during reaction. Theaccumulation of the soluble chromic salts requires either costlyoperations for their removal or increased costs because excessiveamounts of costly chemicals must be used in subsequent operations tooffset this accumulation of the chromic salts. The accumulation of waterfurther complicates the oxidation because it tends to increase thesolubility of the chromic salts and thus further increase costs. It iscommon knowledge in this art that the accumulation of water and chromicsalts in these processes generally retard and stop reaction resulting inlow conversions and poor yields of valuable products. Attempts have beenmade to overcome the accumulation of water by the inclusion of sulfuricacid with the chromic acid.

It is known empirically that the inclusion of sulfuric acid with chromicacid, for example, in an acetic acid solution of steroid derivativesstrongly increases the initial activity of the chromic acid oxidation.Even with moderate concentrations of sulfuric acid there is a largeincrease of acidic organic by-products. Thus Schwenk and Whitman in U.8. 2,244,968 found that chromic-sulfuric oxidation of cholesterylacetate dibromide increased the amount of corresponding by-productcholenic acids several times over that found where chromic acid alongwas used in the usual processes. However the cholenic acids are oflittle value as a by-product in this industry. Similarly Bretschneiderin U. S. 2,246,341 converted cholestenone to 70-80% steroid acids in hisprocess using concentrated sulfuric acid solutions of chromic acid.

While the further disadvantages of low conversion is shown in thechromicsulfuric oxidation of U. S. 2,244,968 by the recovery of a largeamount of starting cholesterol acetate it also shows the additionaldisadvantage of requiring an excessively large amount of zinc dust forthe later debromination step, to overcome the accumulation of chromicsalts in their oxidation mixture. In such manner it is obvious that theinclusion of sulfuric acid in chromic acid oxidations increases costs ofoperations and losses due to excessive destruction of materials eitherto produce non-useful by-product acids, or overcome accumulations ofchromic salts. The use of other acids such as nitric, hydrochloric andthe like results in similar disadvantages.

It also is known in the hormone industry that sulfuricchromic andnitric-chromic tend to destroy the valuable intermediates by furtherdegrading them to steroid acids or tar thereby lowering yields. Attemptsto overcome these disadvantages by working at lower temperatures resultin other disadvantages of decreasing solubilities of reactants andincreased power costs for cooling and mixing.

Further, the strong sulfonating action of sulfuric acid tends torestrict its general use for the oxidation of an-- thracenes andanthraquinones and other aromatic compounds.

It has now been found in accordance with my invention that acommercially advantageous process for the manufacture of selectedvaluable oxygenated organic materials is made available utilizing anoxidizing chromium compound in conjunction with a trivalent chromic ionspecies removing agent. As a result of this continuous removal oftrivalent chromic salts it has been found that the oxidation issteadier, more selective, more complete and proceeds steadily at normaltemperatures. Yields are more satisfactory and a minimum of undesirableby-products are produced when the hexavalent chromium compound oxidationis carried out in the presence of a suitable amount of an orthophosphateproducing compound, for example, phosphoric acid alkali phosphates andthe like which remove the chromic ion from the reaction zone as soon asit forms as an insoluble inert trivalent chromic phosphate. Furtheradditional advantages may be obtained by the utilization of calciumacetate to reduce acidity and remove excess phosphate ion.

As a result of the removal of said trivalent chromic salts the oxidationproceeds steadily and rapidly at convenient temperatures to producesatisfactory conversions and yields of valuable products while at thesame time undesirable side reactions are considerably reduced. When, forexample. the process is used for the degradation of steroid side chainssuch as cholcsteryl dibrom acetate, the major products are thecorresponding dehydroisoandrosterone and pregnenolone suitable for thepreparation of valuable hormones, testosterone and corpus luteumhormone. Similar advantages are gained when the process 18 used toprepare valuable quinones and ketones from appropriate organic rawmaterials such as anthraquinone from anthracene, benzophenone fromdiphenylmethane, and the conversion of 2-methyl anthraquinones to thecorresponding Z-carboxylates. In all these oxidations with this methodthere is immediate and complete removal of trivalent chromium salts fromthe reaction zone and removal from the mixture as solid inert insolublephases to provide resulting large overall conversion of startingmaterial to valuable products while the usual extensive degradation ofstarting materials and products is substantially avoided, because ofsteady but moderate oxidation potentials provided by the combination ofoxidizing chromium and orthophosphate species.

It is an object of this invention to obtain high yields of valuableoxygenated organic synthetic intermediates for hormone, dyestuff,condiment, perfume and the like manufactures by the selective oxidizingchromium compound oxidation of suitable readily available low costmaterials in the presence of orthophosphate producing agents whichcontinuously remove trivalent chromic salts from the reaction zone andsolution during oxidation with the oxidizing chromium compound utilized.

It is also an object of the invention to provide advantageous conditionsfor the oxidation of suitable organic materials by an oxidizing chromiumcompound by utilizing orthophosphotic producing agents for the dualpurpose of supplying both an acidic function and a continuous-removal ofsubstantially all the trivalent chromic salts from reaction zone andsolution as soon as they are produced by reduction.

It is still another object of the invention to maintain particularlyfavorable conditions for the oxidation of suitable organic compounds byan oxidizing chromium compound and an orthophosphate producing agent andfavorable to the production of valuable products, but unfavorable tofurther degradation of valuable products and extensive degradation ofstarting materials while maintaining steady moderate oxidationpotentials and removing trivalent chromic salts continuously and alsoremoving excess oxidizing chromic compounds and excess orthophosphatesfrom the homogeneous reaction mixture.

It is still a further object of the invention to remove from thereaction mixture materials such as trivalent chromic ions, excessoxidizing chromium compound and excess orthophosphate producingcompounds such as by the additional use of calcium acetate in orderreadily to provide separation into portions of substantially onlyorganic constituents which require a minimum of reagents for furtheroperations such as zinc for dehalogenation of halogenated organicproducts, and further readily provide more economical operations whichresult from. the eflicient removal of all inorganic components of themixture as by simple filtration and decantation from inorganicscollected in solid phases.

It is still further another object of the invention to providehydrogen-ion buffered reaction zones by utilizing an oxidizing chromiumcompound in conjunction with mixtures of orthophosphoric acids and theiralkali salts so that while substantially all the trivalent chromiumsalts are removed as an inert solid phase only moderate changes ofhydrogen-ion concentration are possible due to its stabilization by thebuffering action of the phosphates and thus tending to stabilize theoxidation potential which depends on chromic species and hydrogen ionconcentrations. Thus there is uniquely provided buttering systemsthereby which is not possible with sulfuric nitric, hydrochloric and thelike compounds.

In accordance with the invention, suitably protected organic startingmaterials which are dissolved in a suitable inert solvent, for example,acetic acid are treated with an oxidizing chromium compound or chromylcompounds in the presence of an orthophosphate producing compound suchas phosphoric acid, alkali orthophosphates or orthophosphoricanhydrides. Inert solvents such as water, acetic acid, etc., may be usedto dissolve or partially dissolve the chromium and orthophosphatecompounds. When reaction has proceeded to a desired degree, furthertreatment may be made as with calcium acetate to remove excessorthophosphate by converting to insoluble calcium orthophosphates.During oxidation the chromic ion produced by reduction of the oxidant atonce separates out as a readily filtrable insoluble trivalent chromicphosphate thus maintaining the initial substantially trivalentchromic-ion free conditions during oxidation. The oxidant may be addedportionwise over the period of time during which the desired degree ofreaction occurs. Excess of oxidant, if added, may be reduced by suitableaddition of a reductant such as alcohol which converts the oxidizingchromium compound to trivalent chromic, which by conversion toorthophosphate salt results in the removal of substantially all of theadded chromium as an insoluble trivalent chromic phosphate. Sufficientorthophosphate, for example, as phosphoric acid, alkali orthophosphatesor anhydrides is added to remove all the chromium which may form andexcess orthophosphate, if added may be removed as an insoluble calciumphosphate by addition of a suitable amount of calcium acetate or othercalcium salts. When acetic acid is the reaction solvent excess calciumacetate also separates out as a solid phase, thus resulting in completeremoval of inorganic salts.

Thus, at this stage, the new process provides portions containingsubstantially only organic materials including valuable oxidizedintermediates and filtrable and decantable inorganic solids. When inthis process a solution, for example, of halogenated organic products inacetic acid is separated because it is free of inorganics it may bedirectly dehalogenated with a minimum suitable amount of zinc. It isobvious that these separations elfected only by employment of the newprocess increases the over all efficiency of oxidation compared to thegross inefliciency of all the usual chromic acid oxidations. While theusual chromic acid oxidations require costly extractions, purificationof materials or disproportionate amounts of reagents such as zinc toovercome accumulations of chromic salts, the new process considerablyreduces or eliminates these costs.

The simple mixture of organic products which usually is recovered infiltrate may be directly processed with minimum costs to recover itscomponents by usual means i. e., Watering out, immiscible solventextraction, evaporation, alkali washing, semi-carbazone formation, etc.

In this specification and claims, all parts and percentages are byweight unless otherwise indicated.

In order to further illustrate and point out some of the advantages ofthe invention, the following examples are included. These, however, aremerely illustrative and are not to be construed in any way as limitativeof the invention as it is otherwise disclosed and claimed herein.

Example I.-Steroid side chain oxidation To a solution of 3.8 kgm. ofdibromcholesteryl acetate n 138 liters of glacial acetic acid in astirring kettle, there is added portionwise at 35 C. over 1.5 hourschromic anhydride, kgm. 1.3; syrup phosphoris acid, kgm. 8.2; glacialacetic, liters 2.5.

The amount of chromic phosphate triacetic precipitate is used toestimate the degree of completion. Then 0.05 kgm. of methanol is addedand the mixture is slurried with 9 kgms. of calcium acetate. Thesolution of organic products filters free of the chromium, calcium andphosphate salts. The filtrate is treated directly with 0.4 kgm. of zincdust at 50 C., then warmed to 70-80 C. for 2 hours. Low pressureevaporation of the acetic acid from the filtrate and benzene extractionof the solution yields 2.36 kgm. of steroid products from which 0.47kgm. of total acids are removed by alkali extraction and 1.8 kgm. ofneutral oil recovered. The neutral oil assays 0.120 kgm., 6.8%dehydroisoanclrosterone and the total debrominated acids are 16% byWeight of products. X-ray analysis of acids indicates a 3% yield of 3acetoxy A cholenic acid compared to isolation of 12% in U. S. 2,244,968using chromic-sulfuric. The expected amount of chromic phosphatetriacetic precipitate; 4.2 kgms. is found which corresponds to completeremoval.

Example Ia.Deleterius efiects of sulfuric acid increased production ofacidic by-products and extensive degradation 76 gms. ofdibromcholesteryl acetate is dissolved in 3 liters of glacial acetic andtreated with 60 gms. of chromic anhydride mixed with 175 gms. of 85%H3PO4 and 125 gms. of concentrated sulfuric acid. The temperature iskept at 50 C. and reaction is complete in 1.7 hours. The neutral oilrecovery is 47%, while 63% of the cholesterol is converted to acids. Theneutral oil assays (1.05 gm.) 2.8% dehydroisoandrosterone (of theory).This example shows the effect of sulfuric acid to lower yields ofdehydroisoandrosterone (compare Example I) with the extensivedegradation of cholesterol to by-product acids of little value.

Example Ib.Deleterious eflect of H2SO4 31 gms. of dihydrostigmasterol 6dibrom acetate dissolved in 1.2 liters of acetic acid is treated with 24gms. of CIO3 mixed with 76 gms. of 85% HsPO4 and 58 gms. concd HzSOi.The reaction is complete at 50 C. in 1.25 hours. There was a recovery of34% neutral oil which assayed 1.3% dehydroisoandrosterone while 66%conversion of the sterol to acids indicated the property of sulfuricacid to degrade sterols to acid byproducts of little value.

Example Ic.-Deleterious effects of H2804 31 gms. of dibromcholesterylacetate in 1200 cc. glacial acetic, stirred at 50 C., is treated with 70gms. of 85% H3PO4 and 50 gms. of 95% H2804 for 1.1 hours when reactionis complete. The recovery of neutral oil was 8.7 gms. (43.6%) while 56%of the cholesterol was converted to acids. The neutral oil assay is 1.5%dehydroisoandrosterone of theory. These examples utilizing sulfuric acidbring out the deleterious effects of sulfuric in chromic acid oxidationsand point to destruction of valuable ketones (shown by lower yields) andextensive destruction of starting materials to form chiefly valuelessbyproduct acids.

Example lI.Oxidati0n of secondary alcohol with the use of alkalineorthophosphates To gms. benzhydrol dissolved in 200 cc. glacial aceticacid there is added portionwise with stirring over one hour, gms. CrOzmixed with gms. of syrupy A phosphoric (85%) acid and 15 gms. ofNaH2PO4. During oxidation at 30 C. the chromic phosphate-acetic solvateprecipitates out and in two hours reaction is virtually complete. Fivegms. of methanol is added to precipitate out any residual chromium and65 gms. of CrPOr.3CI-IaCOOH is recovered on the filter. The volume offiltrate is 300 cc. after washing the precipitate with acetic. One halfof the filtrate is treated with 14.5 gms. of calcium acetate and theprecipitate is filtered. The recovery of benzophenone after distillationand evaporation is 4.2 gms. The remainder on watering out yields 5.3gms. of crude benzophenone. Crude yield is 94%.

Example lII.Aliphatic side chain oxidation To 10 gms. of diphenylmethanein 200 cc. glacial acetic there is added 85 gms. of 85% syrupyphosphoric acid and portionwise over one half hour 30 gms. of dry CrOz.The temperature is kept at to for 1.5 hours, then raised to C. for tenminutes. Five grams of methanol is added, the chromium is completelyseparated by filtration 99 gms. as a triacetic solvate of chromicphosphate. The organic products are removed by diluting the acetic acidsolution to 2 liters with water and extracted with dichlorethane. Ondistillation of the dichlorethane solvent a residue of 9.9 gms. isobtained. The yield is 9.0

gms. of purified benzophenone, 88% yield of crude benzophenone.

Example IV.Anthracene to quinone, using alkali orthophosphates To 10gms. of anthracene suspended in 200 cc. glacial acetic, there is addedportionwise over one half hour, 30 gms. of CrOa and 60 gms. of NaHzPOidissolved in 125 cc. of water. The temperature is maintained at 30-35 C.and 100 cc. glacial acetic is added. After 1.5 hours, 5 cc. of methanolis added and the chromium salts are completely removed from the reactionmixture by filtration (44 gms. of CI'PO4 is found). The precipitate iswashed with toluene to recover the amberquinone. The filtrate is wateredout to 4 liters, and 10.3 gms. of crude anthraquinone in toluene isrecovered by filtration. On treatment with oleum, the recovery ofanthraquinone was 9.2 gms. yield).

Example V.-Quin0ne to carboxylate To 10 gms. of Z-methyl anthraquinone300 cc. of glacial acetic acid there is added portionwise over 2 hours,30 gms. of CrOa mixed with 200 gms. of syrupy phosphoric acid andoxidized over 3 hours at 60 C. After the addition of 5 cc. of methanolthe chromium salts which are all (98 gm.) in the precipitate arefiltered off and the solution is watered out to recover 11 gms. of crude2-carboxy-anthraquinone. This is recovered in overall yield fromalcohol.

Example VI.C0njugated unsaturation using alkali orthophosphates 19 gms.anethole are dissolved in 200 cc. glacial acetic acid and treatedportionwise with stirring at 35 C. with 51 gms. of 85% syrupy phosphoricacid and 30 gms. of disodium acid phosphate. Over one half hour there isadded 30 gms. CrO dissolved in 40 cc. of water. The reaction is completein 1.5 hours when the CrPO4 3CH3COOH recovered by filtration is 98 gms.The filtrate is watered out to 1.5 liters and extracted withdichlorethane from which the anisaldehyde is recovered as a residue onlow temperature vacuum distillation. Crude yield of anisaldehyde bysodium bisulfite separation is 82%. Anisic acid crude recovery by alkaliextraction of ether solution is 5%.

Example VII 15 gms. of isosafrole treated as in Example VI yields a 87%of piperonal.

Example VIII 15 gms. of acetyl-isoeugenol treated as in Example VIyields 90% of acetyl-vanillin.

Example IX.Ring hydroxyl 5 gms. of 3-hydroxy, 5-6dibromandrosterone-l7-propionate is dissolved in 200 cc. glacial aceticacid and mixed with a slurry of 6 gms. of dry chromium trioxide and 25gms. of 85 syrupy phosphoric acid, with stirring for 1 hour at 30 C. 19gms. of CrPO43CHsCOOH precipitate is recovered on the filtrate aftertreating the reaction mixture with 2 cc. of methanol. The filtrate isslurried with 20 gms. of calcium acetate filtered and directlydebrominated with 8 gms. zinc dust at 50 C. for 2 hours. An 85% yield oftestosterone propionate is recovered from the filtrate.

Example X.Multiple group conversion 5 gms. of 4-isopropyl 4'-propenylbenzhydrol dissolved in 100 cc. glacial acetic acid is treated with aslurry of 18 gms. of dry CrO; and a 75 gms. 85% syrupy phosphoric acidwith stirring for one hour at 30 C. 57 gms. CrPO43CI-I3COOH precipitateis recovered and the filtrate after treating the reaction mixture with 5cc. methanol. The filtrate is slurried with 60 gms. calcium acetate andthe calcium orthophosphate precipitates removed by filtration. 3.2 gms.of 4-aceto 4'-carboxyl benzophenone and 0.5 gm. of 4-aceto 4-forrnalbenzophenone are recovered by watering out and selective extraction withether and separation into acidic and neutral fractions.

The new process, the invention, is noted in the examples to becharacterized by immediate, continuous and substantially completeremoval of trivalent chromium as an inert solid phase. The insolubletrivalent chromic phosphate may be solvated, for example, with three tosix molecules of acetic acid when concentrated acetic acid is used. As aresult, in the invention method, characteristically, the reaction zonesin the solution are substantially freed of trivalent chromium ion andtherefore freed of the interference which the trivalent chromium ion orsalts thereof when present in the solution are known to exert on therate and extent of the oxidation reaction. It is probable that withreaction zones freed of trivalent chromium ion species these conditionsfavor a steady rate of oxidation which tends to drive the oxidationreaction to completion. This contrasts with the usual chromic acidoxidations which are known generally to decrease in rate as thetrivalent chromium concentration increases and stop the reaction. In thenew process due also to hydrogen ion buffering property of mixtures ofphosphoric acids and salts, the hydrogen ion concentrations also tend tobe stabilized which, of course, is not possible with, for example,sulfuric-chromic, nitric and hydrochloric and the like mixtures, withtheir salts because sulfuric acid and the like cannot form bufferingsystems. Substantially no tar, nor the like forms, and by-products suchas those produced by sulfonation and polymerization with sulfuric acidand extensively degraded products do not form, as by the use ofsulfuric, nitric hydrochloric and the like. The oxidizing chromiumcompound in the presence of orthophosphoric acids, because of moderateoxidation potentials does not tend to degrade carbonyls of ketones whichare the valuable intermediates nor tend to degrade carboxylic acids.This contrasts with chromic-sulfuric and other acid oxidations which areknown, for example, U. S. 2,246,341 to vigorously attack ketones andextensively degrade acids by vigorous attack of carboxyl groups.

The new process provides characteristically the immediate continuous andcomplete removal of trivalent chromic ion from the reaction zone andsolution wherein said trivalent chromic ion is formed by reduction ofoxidizing chromium salts by suitable organic compounds and converted byorthophosphates to solid insoluble phase. It tends to stabilize aciditydue to buffering properties of mixtures of orthophosphoric acids andtheir salts. The oxidations generally proceed satisfactorily andsteadily at normal temperatures or with moderate heating. In general theadvantages which uniquely depend on and result from the orthophosphatesare efficient and complete utilization of oxidizing chromium compound,stabilized vigor and steady rate of oxidation, stabilized acidity,avoidance of extensive degradation of valuable products and theefficient separation of chromium orthophosphate salts from the reactionzone and mixture.

These advantages result in economics in operation by providing mixturesreadily separable by simple filtration or centrifugation and decantationto isolate the organic components and further economies by reducing theamounts of processing materials such as zinc for dehalogenation whenhalogenated products, for example, are produced as in the usual steroidoxidations. The increased conversions also provide economies in rawmaterials. These comprise the new and useful results afforded by theinvention.

The new process employing an oxidant comprising an oxidizing chromiumcompound and an orthophosphate producing compound which may be used inconjunction with calcium acetate is applicable generally to theselective oxidation of carbon-hydrogen bonds for which oxidantscontaining hexavalent chromium such as chromic trioxide, a bichromate,chromate and a chromyl compound are suitable. Some examples ofsubstrates which are suitable: ethylenic compounds such as 1:1 diphenylethene; 5,6 dibrom stigrnasterol acetate (side chain oxidation of doublebond), anethole, isosafr ole, isoeugenol; suitable primary and secondaryalcohols such as benzhydrol, 4 isopropyl 4'propene benzhydrol, the3-hydroxy steroids, hexanol, butanol and cinnamyl alcohol; suitablealdehydes such as heptanal, butyral, phenylacetaldehyde; suitablehydrocarbons such as diphenylmethane, 2-methyl anthraquinones,anthracenes and sterolic side chains which may include suitablyprotected coprosterols, dihydrochloresterols, phytosterols such asstignasterol, sitosterol and the like. These organic compounds which arecontemplated as suitable for the new process may be defined in terms oftheir chemical compositions to have hydrogen directly attached to a nonoarbonylated carbon atom whose bond is oxidatively attacked. Thus whilethe above types are suitable, such compounds as oxalic acid andcarboxylic acids, ketones and tertiary a1cohols such as tertiary butylcarbinols and certain unsaturated compounds having no hydrogen on thecarbon forming the unsaturated bonds such as tetramethylethene are notcontemplated to fall within the scope of the invention. Certain of saidsuitable materials such as the 4-isopropyl. 4-propenyl benzhydrol andsteroids because they contain polyfunctional groups of the specifiedtype may be converted by attack simultaneously of several of the groupswhen treated in accordance with the method of the invention. Thus4-isopropyl, 4propenyl benzhydrol is converted as in Example 10.Suitable compounds are those having a hydrogen containingnoncarbonylated carbon atom in a group of C, H and O atoms, and saidcarbon atom is oxidatively attacked and converted to carbonylatedderivatives.

When a solvent is used it should be inert to the oxidant. Examples ofsolvents that may be used are acetone, tertiary butyl carbinol and thelike, and preferably acetic acid may be used.

Starting materials which have two or more groups susceptible tooxidation such as the sterols, may be protectively saturated byhalogenation, etc., or acylated or halogen substituted for the hydroxylgroup. Thus oxidation suitably may be confined to the carbon hydrogenbonds of the side chain or alternatively such as 3-hydroxy-17-keto-5-6halogenated steroids (secondary alcohols may be oxidized to the 3-ketoderivatives. Thus products which have the appropriate alcohol orethylenic bond functions may be protected in known manner and the OH anddouble bond restored by hydrolysis and dehalogenation with zinc or otherknown dehalogenating agents.

While the oxidizing chromium compound may be added in the anhydrous formsuflicient water or other inert solvent may be added to bring it intosolution. Phosphoric compounds which supply an orthophosphate ion in thereaction system may be used, such as mono and diacid phosphates,phosphoric anhydri-de, metaphosphoric or pyro-phosphoric acids.Orthophosphoric acid is preferred. The term phosphoric acid appearing inthe claims include all these phosphoric materials.

The amount of phosphoric acid to be used is related to the amount ofchromic ion formed during the oxidation reaction (by reduction of theoxidizing chromium compound) and should be at least suflicient to removeall the chromic ion as it formed. In general a ratio of one to fourmoles of phosphate to one of oxidizing chromium compound is preferred.

I claim:

1. In a method for the oxidation of an organic compound having ahydrogen attached to a carbon by means of a chromic oxidizing agent inan inert oxygenated organic solvent to produce a correspondingcarbonylated compound, the improvement which comprises carrying out saidoxidation in the presence of the orthophosphate group whereby by-producetrivalent chromium is substantially removed from the solution as formedas a solid chromium phosphate.

2. A method of claim 1, carried out at a temperature of about 30 toabout 60 C.

3. A process of claim 2, wherein anthracene is oxidized toanthraquinone.

4. A process of claim 3, using chromium trioxide in aqueous acetic acidand a mixture of orthophosphate and alkaline orthophosphate.

5. A process of claim 2, wherein the hydrogen is attached to anethylenic carbon atom, and a corresponding benzaldehyde is obtained.

6. A process of claim 5, applied to an alpha-beta unsaturated phenylpropene using chromium trioxide, acetic acid and a mixture oforthophosphoric acid and alkaline orthophosphates.

7. A process of claim 2, wherein the hydrogen is part of the methylgroup in a methyl anthracene and the corresponding carboxy anthraquinoneis obtained.

8. A process of claim 7, applied to a 2-methyl anthracene using chromiumtrioxide, glacial acetic acid and orthophosphoric acid.

9. A :process of claim 2, wherein the hydrogen is attached to a tertiarycarbon in a steroid molecule and the corresponding ketone is obtained.

10. A process of claim 9, applied to a dihalocholesterylacyl ester usingchromium trioxide, .acetic acid and orthophosphoric anhydride followedby treating the References Cited in the file of this patent UNITEDSTATES PATENTS 1,405,954- Thatcher Feb. 7, 1922 1,998,925 Demant Apr.23, 1935 2,202,063 Ogilvie May 28, 1940 2,256,449 George Sept. 16, 1941FOREIGN PATENTS 3,180 Great Britain of 1879 7,631 Great Britain of 191026,432 Great Britain of 1910 OTHER REFERENCES Hinnemann: Annalen, V133,pp. 10, 11 (1865). Balfour et al.: J. Chem. Soc., 1935 (pp. 1723-8).

1. IN A METHOD FOR THE OXIDATION OF AN ORGANIC COMPOUND HAVING AHYDROGEN ATTACHED TO A CARBON BY MEANS OF A CHROMIC OXIDIZING AGENT INAN INERT OXYGENATED ORGANIC SOLVENT TO PRODUCE A CORRESPONDINGCARBONYLATED COMPOUND, THE IMPROVEMENT WHICH COMPRISES CARRYING OUT SAIDOXIDATION IN THE PRESENCE OF THE ORTHOPHOSPHATE GROUP WHEREBYBY-PRODUCTS TRIVALENT CHROMIUM IS SUBSTANTIALLY REMOVED FROM THESOLUTION AS FORMED AS A SOLID CHROMIUM PHOSPHATE.